Coated stent with geometry determinated functionality and method of making the same

ABSTRACT

The present invention, in an exemplary embodiment, provides a stent, which combines many of the excellent characteristics of both silicone and metal stents while eliminating the undesirable ones. In particular, a principal objective in accordance with the present invention is to provide a family of stents where the relative hardness/softness of regions of the stent can differ from other regions of the stent to provide additional patient comfort and resistance to compression forces. Exemplary embodiments provide a stent that is coated in a manner that limits the amount of coating surface area that is in direct contact with the target lumen. In particular, a covered stent is provided that is coated internally such that the outer scaffolding surface of the stent is raised from the outer surface of the coating. To this end, cilia function is only partially limited and mucociliary clearance is not significantly affected. Moreover, the coating itself has anti-adherent properties such that bacteria, fungi or other microbials cannot colonize the cover in particular and the stent generally.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application is a divisional application of U.S.Non-provisional application Ser. No. 10/669,450, filed Sep. 24, 2003,which is a continuation in part of and claims the benefit of priorityunder 35 U.S.C. §120 to co-pending U.S. Nonprovisional application Ser.No. 10/288,615, filed Nov. 5, 2002, which is incorporated in itsentirety by this reference.

FIELD OF INVENTION

The present invention relates generally to medical devices directed tothe prevention of luminal occlusion, and more particularly to stents andmethods for making and utilizing these stents in the treatment of bothbenign and malignant conditions wherein the functionality of the stentsis determined by geometrical variability of the scaffolding andconcomitant interstices.

BACKGROUND OF THE INVENTION

Stents are devices that are inserted into a vessel or passage to keepthe lumen open and prevent closure due to a stricture, externalcompression, or internal obstruction. In particular, stents are commonlyused to keep blood vessels open in the coronary arteries and they arefrequently inserted into the ureters to maintain drainage from thekidneys, the bile duct for pancreatic cancer or cholangiocarcinoma orthe esophagus for strictures or cancer. Vascular as well as not vascularstenting has evolved significantly; unfortunately there remainsignificant limitations with respect to the technology for producingstents suitable to various portions of a patient's anatomy.

Historically, in order to provide a stent with varying characteristics,the stent had to be manufactured from multiple materials, at least onefor each characteristic desired. As a result, many of these stents arewoven from two or more metals having differing shape-memories forexample. Unfortunately, braided stents are vulnerable to prematureobsolescence. Moreover, providing multiple material types in a singlestent may lead to inconsistent characteristics along the surface area ofthe stent. This is particularly undesirable when the stent is to beplaced in vascular or nonvascular lumens that have been occluded for onereason or another. The stent needs to be stiffer in some regions whilemore flexible in others.

Additionally, medical device companies have identified the need to coverstents at least partially to prevent the epithelialization of thescaffolding. Most covered stents however have an elastomeric cover thatis subject to bunching particularly about stenotic tissue. This can leadto additional tissue granulation. Alternatively, the stents are dipcoated which can lead to uneven coating as well as inconsistency instent performance from batch to batch.

Additionally the ends of the stent tend to be exposed in order toencourage granulation tissue formation, which helps to anchor the stentin place. With metal stents, the direct metal to tissue contactaccelerates tissue granulation and galvanic current generation is alsoan undesirable byproduct. Such direct current can have indirect effectson tissue granulation and direct effects on fluid flow dynamics.

Moreover, since many medical device companies have chosen to use poorlyadapted cardiovascular stents for Pulmonary, GI and Peripheral Vascularindications, many of the anatomical differences in the lumens are notaccounted for in stent design. For example, the pulsation of thecardiovascular lumen and the concomitant radial force requirements of acardiovascular stent differ substantially from that of a tightlyconstricted lumen such as the trachea during repeated coughing. When astent developed for the former is indicated for the latter, the stenttends to fail under the extreme conditions and lose its elasticity andtherefore its ability of ensure airway potency. Non-vascular lumens alsotend to have ciliated epithelia so as to facilitate clearance of fluidsand particulates. As a general principal, coated stents were notspecifically designed for ciliated lumen in that the external coatingdamages the cilia and prevents the body's natural clearing function.Moreover, the coating itself is usually made of a predominatelyhydrophilic polymer, which can lead to mucous formation and/or fluidstagnation. Stagnation of fluids or material passing through the lumencan lead to additional complications such as in stent restenosis orbacterial infections.

Therefore, there remains an existing need for a therapeutic stent thatcan have varying characteristics along its surface area while beingstamped, not braded, from a single base material. Moreover, there is aneed for such a therapeutic stent where the relative hardness, softness,flexibility, stiffness and radial force can be modified as a function ofgeometric considerations rather than material considerations. Inparticular, there is a need for a stent that is divided into zones so asto allow the stent to have predetermined characteristics in one zone andcould conceivably have drastically different characteristics in anadjacent zone so as to allow for stents that can be tailored toanatomical lumens in general and the particular lumen topography of aspecific patient in particular. An additional need remains for a stentthat is coated in a manner that limits the amount of coating surfacearea that is in direct contact with the target lumen. In particular,there is a need for a covered stent that is preferably coveredinternally such that the outer scaffolding surface of the stent israised from the outer surface of the coating. To this end, ciliafunction is only partially limited and mucociliary clearance is notsignificantly affected. A need also remains for a coating that itselfhas anti-adherent properties or is complexed with an anti-adherent suchthat bacteria, fungi or other microbials cannot colonize the cover inparticular and the stent generally.

SUMMARY OF EXEMPLARY EMBODIMENTS

It is a principal purpose of the present invention to provide a stent,in accordance with an exemplary embodiment of the present invention,which combines many of the excellent characteristics of both siliconeand metal stents while eliminating the undesirable ones. In particular,it is an objective of a preferred embodiment in accordance with thepresent invention to provide a stent that is easily installed, yet inalternative embodiments, removable. Moreover the stent in accordancewith this embodiment of the present invention would not cause materialinfections and may be capable of reducing infection. Therefore, aprincipal objective of a preferred embodiment in accordance with thepresent invention is to provide a prosthesis that is suitable for bothpermanent and temporary use while being easy to insert, reposition andremove.

A principal objective of a preferred embodiment of the present inventionis to provide a stent that may be stamped from preferably a singlematerial that is capable of maintaining its axial working length whenradially compressed. To this end, the stent does not have a seam thatcould aggravate luminal tissue. In particular, a stent in accordancewith the present invention is formed using a tool that molds the stentsouter contour as well as its interstices.

It is yet another objective of an exemplary embodiment of the presentinvention to provide a stent that can be indicated for the treatment ofbenign and malignant disease and improve the way clinicians treatmalignant obstructions.

Still another objective of the present invention is to provide a stentand method for installing the stent that is economical and suitable forroutine purposes. Moreover, the stent will have minimal migration, causeminimal tissue granulation, will not foreshorten after deployment andmucociliary clearance will not be problematic.

Yet another objective of an exemplary embodiment in accordance with thepresent invention is to provide a prosthesis that will have superiorinternal to external diameter ratio, superior radial force with dynamicexpansion, while being suitable for use in pediatric and adult patientswith malignant and benign disease.

A principal objective of an exemplary stent in accordance with thepresent invention is to provide a family of stents where the relativehardness/softness of regions of the stent can differ from other regionsof the stent to provide additional patient comfort and resistance toradial forces.

An additional objective in accordance with an exemplary embodiment is toprovide a family of stents with novel interstice configurations thatfacilitate flexibility, durability and/or proper installation.

Still another objective of a preferred embodiment of the presentinvention is to provide a self-expanding stent having the above benefitsthat also defines a plurality of apertures at the termini of the stentfor, inter alia, removal of the stent.

An additional objective in accordance with a preferred embodiment of thepresent invention is to provide a prosthesis that minimizes ciliadestruction at the site of implantation. In the furtherance of this andother objectives, the preferred prosthesis is coated internally with apolyurethane such that the surfaces of the struts that come into contactwith the lumen of the patient are elevated above the surface of thecoating such that the cilia can move to allow for free fluid action ofciliated epithelium.

Further objectives, features and advantages of the invention will beapparent from the following detailed description taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows a polarization microscopic image of a plurality of zones ofa stent in accordance with a preferred embodiment of the presentinvention.

FIG. 2 shows an alternative perspective view of the polarizationmicroscopic image of FIG. 1.

FIG. 3 shows an enlarged perspective view of the interstices of anexemplary zone as shown in FIG. 1.

DETAILED DESCRIPTION OF AN EMBODIMENT

A preferred embodiment of the stent, in accordance with the presentinvention, provides a stent that prevents epithelialization of the stentand is not subject to premature elongation and foreshortening but iscapable of engaging the desired implantation location. The stent alsoretains its axial length while undergoing radial compression.

The stent is preferably formed from a composite material selected fromthe group consisting essentially of Ni, C, Co, Cu, Cr, H, Fe, Nb, O, Tiand combinations thereof. The composite material is generally formedinto a compressed tube from which the stent is etched and is formed on asuitable shaping device to give the stent the desired external geometry.Both the synthetic collar techniques and in vitro valuation techniquesshow the remarkable ability of stents in accordance with the presentinvention to convert acting force into deformation work absorbed by theangled structure, which prevents excessive scaffolding stress andpremature material fatigue and accelerated obsolescence.

Though one skilled in the stent engineering art, once apprised of thepresent application, would be able to manufacture a stent consistentwith the present invention by other methods, a preferred method ofmanufacturing such stents follows. As stated above a composite materialis selected and a blank is formed there from. The blank is preferablylaser etched and the etch work is generally verified for accuracy usingvisual recording microscopy. Dimensional measurements are taken toensure strut thickness, segment angles, zone placement, etc. Moreover,the stent is preferably formed on a shaping tool that has substantiallythe desired contour of the external stent dimensions.

In the event the stent is to be shaped to the dimensions of a particularlumen, optical photography and/or optical videography of the targetlumen may be conducted prior to stent formation. The geometry ofcorresponding zones and connector regions of the stent then can beetched and formed in accordance with the requirements of that targetlumen. For example, if the stent were designed for the trachea, whichhas a substantially D shaped lumen and additionally the middle zonesneeded to be softer than the end zones, the stent could be designed tothose specifications. With specific reference being made to FIG. 1, itcan be seen that angles α, β, δ, ε and γ may be modified to providedifferent characteristics to different zones of the stent. Inparticular, if the topography of the trachea of a particular patient iscaptured optically and the appropriate dimension provided, a patientspecific prosthesis could be engineered. These techniques can be adaptedto other non-vascular lumen but is very well suited for vascularapplications where patient specific topography is a function of avariety of factors such as genetics, lifestyle, etc.

It should be pointed out that unlike the use of differing shape memorymaterials to change regions of a stent, stents in accordance with thepresent invention can take on an infinite number of characteristiccombinations as zones and segments within a zone can be modified bychanging angles, segment lengths and segment thicknesses during theetching and forming stages of stent engineering or during post formationprocessing and polishing steps. Moreover, by modifying the geometry ofthe connectors between zones, additional functionality may be achieved.

Exemplary stents 10 in accordance with the present invention are shownin FIGS. 1-3 showing the preferred interstice geometry. Not shown are awide variety of interstice geometries that are also acceptablealternatives to the preferred, namely, U, V, W, Z, S and X geometries toname a few.

The stent 10 also is formed of memory metal and preferably has uniquegeometrical interstices that are laser etched therein. However, otherconventional ways of forming interstices in unitary scents, though notequivalent are contemplated, may be employed and would be within theskill set of one in the art.

It cannot be overemphasized, however, that this does not mean theknowledge that changes in the geometry of interstices affect stentfunctionality is currently known in the art. To the contrary, thepresent inventors discovered the interrelation between intersticegeometry, width, length and relative resistance to torsional stress andradial force. In fact, it can be said that the stent 10 hascircumferential bands extending perpendicularly with respect to theluminal device's longitudinal axis. These bands are referred togenerally as zones. A connector 50 connects these bands to one another;the connector 50 is an additional means for adjusting stentfunctionality. In particular, the connector 50 defines a substantially Ushaped member, but could define other geometries such as U, V, W, Z, Sand X to name a few. As shown specifically in FIG. 1, δ, ε and γ vary inshape and that the corresponding region of the stent differs infunction. It can also be seen from FIG. 1, at least one but preferably aplurality of eyelets φ that allow a physician to purse string the stentwith suture to facilitate removability. The eyelets are preferablybetween about 200 μm and 300 μm, however, the eyelets may be smaller orlarger to accommodate the need of the target site. The preferred eyeletsize is about 350 μM as the preferred suture type is 4-0. The medicalappliance may be pre-threaded with suture or the user may provide thesuture after implantation.

In a standard orientation, as shown particularly in FIG. 2, thesubstantially U-shape connector comprises preferably two leg members 52& 56 and a crossing member 54 that connects with and extendsperpendicularly at preferably 90° angles with respect to the leg members52 & 56. It must be noted that alternative angles may be providedwithout departing materially from the invention. The present inventorsdiscovered that if you modify the length of the crossing member 54and/or the leg members 52 & 56 and/or the angle γ at which the crossingmember 54 and the leg members 52 & 56 intersect, the relativehardness/softness, radial force and/or flexibility of the stent 10 couldbe modified. The angles γ can be modified at varying acute angles shortof 90° or varying obtuse angles greater than 90°. The incrementalchanges correspondingly change certain characteristics of the stent 10.As a result, different zones of the stent 10 can be given differentrigidities to improve patient comfort and for example, in airway stents,to facilitate luminal patency. Moreover, various anatomical lumens mayneed different degrees of stent rigidity. As a result, stents 10 inaccordance with the present invention can be manufactured to exactingspecifications to contour properly to various lumens in a patient'sanatomy, which may need varying levels of structural support from themedical appliance.

Referring now to FIG. 3, there is an enhanced capability provided bystents in accordance with the present invention. By adjusting thedistance between the connector 50 and the zones between which connector50 resides, the way in which the stent reacts to strain can be modified.By way of non-limiting example, if the connector 40 is oriented closerto one zone than to another zone, the stent will be less flexible and beable to withstand greater radial force. Alternatively, if the connectoris equidistant between zones, the stent will be more flexible and beable to withstand less radial force. Please note that these differencesare relative to a neutrally located connector 40. The behavior is afunction of distance and as a result varies along a continuum withrespect to the connector's orientation between the medium between zonesand the tip of each zone. Moreover, within by varying the number ofconnectors 40 that connect the zones to one another, functionality canbe impacted. In particular, the fewer the number of connectorsconnecting the zones the more torsional flexibility the stent will have.The converse will generally hold true with respect to a greater numberof connectors.

Connector 40, which serves a similar purpose as connector 50 also has acrossing member 44 that connects leg members 42 & 46 at a predeterminedangle δ. As discussed above, since form follows function for stentsprepared through this novel method, by changing the degrees of angles α,β, δ& γ, stent characteristics can be modified. Moreover, by changingthe leg lengths of all the previously discussed legs or individual legsseparately, additional stent characteristics can be obtained. The beautyof this system is that the desired characteristics can be determinedprior to forming the stent and by staying within certain formingparameters, the stent can be formed, crimped, delivered and deployedwith confidence that the desired functionality with result. This isimportant in light of the fact that both vascular and nonvascular lumenhave unique topography. As a result, methods and devices in accordancewith the present invention usher in the ability to tailor prosthesis toanatomical tissue in general and particular patient anatomy inparticular.

The U shaped connectors 40 & 50 have a crossing member and at least twoleg members, respectively. The present inventors discovered that if youincrease/decrease the length of leg members and/or increase/decrease thelength of crossing members and/or vary the angle at which crossingmembers and leg members intersect, you affect the functionality of thestent. In particular, the shorter the length of the leg members, theless flexibility available in that portion of the stent. Takingparticular note of FIG. 3, by way of example only, if you want todecrease the amount of torsional flexibility of the stent 10, you wouldhave to modify the connector 40 so that the legs 42 & 46 are longer thanshown and that the angle δ formed by legs 42 & 46 and crossing member44, respectively, is slightly greater than 90°. Alternatively, thelength of the crossing member 44 can impact the functionality of thestent as well. The stent can be made more rigid by shortening crossingmember 44 or the stent may be made more flexible by lengthening crossingmember 44. It should be noted that the combination of the changes of leglengths, crossing member lengths, angle variations, shapes and number ofconnectors provide the stent with the ability to conform to specificlumens in the anatomy of a patient. The result is a form fitting medicalprosthesis that may be tailored to specific anatomical lumens in generaland to the anatomical lumens of an individual patient in particular.

In a preferred embodiment, the modification of interstice geometries andmanipulation of the U shaped connection member to achieve variable stentfunctionality is provided. The rigidity of the stent scaffolding orinterstice matrix along with the torsionality of the stent itself isprincipally a function of these modifications. In an exemplaryembodiment, the stents relative flexibility can be rated soft, medium orhard based on the degree of flex and torsionality. The less torsionalityand flex in the stent the harder the stent is rated.

An exemplary stent in accordance with the present invention withrelatively great torsionality and radial flexibility would be ratedsoft. An exemplary soft rated stent comprises distance between U shapedconnectors of about 45 μm in the compressed state (i.e., contracted inthe 3 mm tube subject to laser etching). Moreover, the length of thecrossing member is preferably about 1.0 μm. The lengths of the legmembers are preferably about 1.5 μm long. Additionally the leg membersmay further comprise feet that attached to the remainder of the stentscaffolding. The feet can be adjusted from a standard length of about0.25 μm to further adjust the characteristics of the stent. There isadditionally a substantially rectangular member incorporated in the Ushaped connector with similar capacity for variability. The variabilityfactors and results of modifying the dimensions of the substantiallyrectangular members are similar to those evinced by leg lengthdimensional modifications.

By way of example, but not to be construed in any way as limiting, thesoftness index or relative flexibility can be increase by increasing thevarious lengths discussed above. For example, by increasing the lengthof the legs and crossing members of the U shaped connector, flexibilityincreases. However, with respect to the distance between U shapedmembers and distance between interstices in a preferred stentembodiment, there is an inverse correlation between length and softness.This relative softness/hardness indexing as a corollary of intersticedimensions is a novel aspect of preferred embodiment of the presentinvention. As a practical rule of thumb, longer leg lengths coupled withacute angles provide for greater flexibility. Conversely, shorter leglengths and more obtuse angles provide more rigidity. By way ofnon-limiting example, a U shaped connector with short legs deviatingfrom the crossing member at angles greater than 90°, will be extremelyrigid and resistant to torsional strain as compared to a U shapedconnector with longer legs diverging from the crossing member at anglesless than 90°.

In addition to the length and spacing differences, the intersticesthemselves may define various shapes that by their very nature affordnovel functionality to the stent. The changes of functionality, however,are more a function of the dimensional differences of the various shapesrather than a function of the shapes themselves. Therefore, it isimportant to keep in mind that the dimensional differences discussed inthe previous paragraph are determinative of the functionality accordedthe stent by the varying interstice geometries. It is for this reasonthat one of ordinary skill in the art, after being apprised of thepresent invention, would be able to conceive of a number of intersticegeometries to satisfy certain functionality criteria by keeping certaindimensional parameters constant.

FIGS. 1-3 also show the coating provided in select embodiments inaccordance with the present invention. The coating 100 preferablycomprises a stable polymeric material such as polyurethane that can bedeposited on a stent to form a thin film. The film preferably formslayers when annealed to the stent such that the hydrophobic moietieswithin the polymer are predominately oriented outward and thehydrophilic moieties are predominately oriented inward. It should benoted that depending on the characteristics desired by the user, therelative hydroaffinity may be altered. For example, in the event theimplant was placed with the intention of collecting mucous in therespiratory system, the coating 100 would more suitably have apredominately hydrophilic outer surface. Moreover, by manipulating thehydroaffinity of the coating 100, the physiochemical parameters such assurface-free energy, charge density provide a substantial barrier tobiofilm formation in general and ligand-binding events mediated bymicrobial adhesions and extracellular polymers. However, additionalanti-adherents know in the art may be applied to provide lubricity aswell as an additional barrier for microbials. For example, a preferredcoating 100 in accordance with the present invention would behydrophilic and hydroscope to ensure the surface would always be wetwhich prevents mucostasis as well as microbial adherence.

Regardless of desired coating surface characteristics, preferred stentsin accordance with the present invention are coated from the interior ofthe stent lumen such that the stent scaffolding is raised about between1 Å to 10⁶ Å above the surface of the coating 100 as shown in FIG. 3 asindicia 200. One of the principal functions of such architecture is tofacilitate cilia action by allowing cilia movement between stent struts.

The stent is preferably coated in a multi-step process, which comprisesproviding a stent and initially spraying the stent with a polymericmaterial to coat the struts. Though the steps may be reversed it ispreferable to follow the spraying step with the interior coating step.In particular, the stent is placed into a hollow mold to retain thestent shape as the internal diameter of the stent is coated with thepolymeric material to form a non-porous coating 100. The coating 100 canbe provided in sheets or additional spray applications, however, thepreferred embodiment is the sheets. Sheets are generally preferred tofacilitate the proper orientation of the polymer side chains to ensurethat the desired moiety (e.g., hydrophilic and/or hydrophobic) is facingthe lumen. Once the layer of polymer is introduced into the innerdiameter of the stent, a balloon or other device in which temperaturecan be regulated is implanted to sandwich the layer of polymer betweenthe stent inner diameter and the balloon. The balloon is expanded andheated to a temperature of about between 200° and 400° F. to anneal thepolymer to the stent. Preferred polymers such as various designerpolyurethanes (e.g., Cronoflex® manufactured by CardiotechInternational) are suitable for such applications but other polymers areacceptable.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrative,and not restrictive. The scope of the invention is, therefore, indicatedby the appended claims, rather than by the foregoing description. Allchanges, which come within the meaning and range of equivalency of theclaims, are to be embraced within their scope.

1. A method of coating a medical appliance comprising the steps of:providing a medical appliance comprising a scaffolding of strutsdefining a substantially cylindrical member having a distal end and aproximal end and a lumen extending longitudinally therebetween, thescaffolding having an interior and an exterior surface along itslongitudinal extension; and applying a polymer to the medical appliancesuch that the exterior surface of the scaffolding is raised with respectto the polymer extending substantially over an area between the strutsof the scaffolding.
 2. The method of claim 1, further comprisingannealing the polymer to the stent by applying heat to the polymer. 3.The method of claim 1, wherein applying comprises applying a polymer tothe exterior surface of the scaffolding.
 4. The method of claim 1,wherein applying comprises applying a polymer to the interior surface ofthe scaffolding.
 5. The method of claim 1, wherein providing comprisesproviding a medical appliance further comprising an additional distalend wherein the medical appliance forms a substantially Y-shape.
 6. Themethod of claim 1, further comprising spraying the medical appliancewith a polymer prior to applying the polymer to the medical appliance.7. The method of claim 1, further comprising providing a mold having aninternal and an external diameter and inserting the medical applianceinto the internal diameter of the mold.
 8. The method of claim 7,further comprising applying a polymer to the interior surface of themedical appliance.
 9. The method of claim 8, further comprising:inserting a balloon within the internal diameter of the mold; andexpanding and heating the balloon to anneal the polymer to the medicalappliance.
 10. The method of claim 1, wherein the polymer issubstantially hydrophobic.
 11. The method of claim 10, wherein thepolymer is hydroscopic.
 12. The method of claim 1, wherein the polymeris substantially hydrophilic.
 13. The method of claim 12, wherein thepolymer is substantially hydroscopic.
 14. The method of claim 1, whereinapplying comprises applying the polymer to the medical appliance fromthe interior surface of the scaffolding outward.
 15. The method of claim1, wherein applying comprises applying the polymer to the medicalappliance from the exterior surface of the scaffolding inward.
 16. Themethod of claim 15, wherein applying comprises applying the polymer tothe medical appliance such that the struts on the exterior surface ofthe scaffolding are raised with respect to the polymer applied betweenthe struts of the medical appliance.
 17. The method of claim 16, whereinapplying comprises applying the polymer such that the polymer applied tothe struts of the scaffolding is raised between 1 Å to 10⁶ Å withrespect to the polymer applied between the struts of the scaffolding.18. The method of claim 16, wherein applying comprises applying thepolymer such that the relative extent to which the polymer applied tothe exterior surface of the scaffolding is raised with respect to thepolymer applied between the struts facilitates cilia function at thecite of implantation.